Lactase protein is a disacharidase (β-galactosidase) expressed on the tips of the villi of the small intestine having the ability to hydrolyze lactose into galactose and glucose. Inadequate lactase-phlorizin hydrolase (LPH) activity is responsible for lactose intolerance/malabsorption leading to diarrhea, abdominal pain or bloating after lactose ingestion. Primary lactase deficiency (or lactase non persistence or hypolactasia) is the main cause of lactose intolerance, due to the relative or absolute absence of lactase expression in the small bowel, occurring in childhood at various ages and in different racial groups Approximately 70% of the world's population has primary lactase deficiency. The percentage of lactose deficiency varies according to ethnicity and is related to the use of dairy products in the diet reaching up to 20% of North European, 40% of Mediterranean European, 80% of Africans, and 90% of Asian population. Typical treatments for lactose intolerance is lactose exclusion (leading to nutritional impairment) or expansive regimen such as the use of lactose deficient milk or lactase supplementation.
It has been reported that two particular Single Polymorphisme (SNP) nucleotide are tightly associated with adult-type hypolactasia. A C at position—13910 (C—13910) upstream of the lactase gene is 100% associated and a G at position—22018 (G—22018) is more than 95% associated with lactase non-persistence in the Finnish population. SNP. Expression of LPH mRNA in the intestinal mucosa in individuals with T—13910 and A—22018 is higher than found in individuals with C—13910 and G—22018, suggesting a transcriptional regulation of LPH gene. However, much of the regulation of the LPH gene remains unknown. Accordingly, effective agents, that are useful in the treatment of lactose intolerance and related disorders are needed.
Peroxisome Proliferator Activated Receptors (PPARs) are members of the nuclear hormone receptor super family, which are ligand-activated transcription factors regulating gene expression. PPARs play a role in the regulation of cell differentiation, development and metabolism of higher organisms.
Three types of PPAR have been identified: alpha, expressed in the liver, kidney, heart and other tissues and organs, beta/delta expressed for example in the brain, and gamma, expressed in three forms: gamma1, gamma2, and gamma3. PPARγ receptors have been associated with stimulation of keratinocyte differentiation, and has served as a potential drug target for a number of disease states including skin disorders such as psoriasis and atopic dermatitis.